Single dose recombinant bovine fsh after follicular synchronisation

Abstract

The present invention relates to methods and compositions for increasing reproduction performance in non-human mammals using a biologically active recombinant Follicle Stimulating Hormone (rFSH). The invention also relates to methods for increasing ovulation, embryo production or pregnancies in non-human mammals using rFSH. The invention may be used in particular in ungulates such as bovines or equines.

We claim: 
     
         1 . A method for increasing reproductive performance in a non-human mammal, comprising administering to said non-human mammal a recombinant FSH (rFSH) analog, or a composition comprising an rFSH analog, wherein said rFSH analog is administered to said non-human mammal after follicle synchronization and in one single administration. 
     
     
         2 . The method of  claim 1 , wherein the rFSH is administered in one single administration at a dose range between about 0.01 μg and about 5 mg. 
     
     
         3 . The method of  claim 2 , wherein the rFSH is administered in one single administration at a dose range between about 1 μg and 2 mg, or between about 10 μg and 1 mg. 
     
     
         4 . The method of  claim 3 , wherein the rFSH is administered in one single administration at a dose of 50 μg or 100 μg. 
     
     
         5 . The method of  claim 1 , wherein said rFSH is administered by systemic administration. 
     
     
         6 . The method of  claim 1 , wherein said rFSH analog comprises an alpha subunit having a sequence of a non-human mammal FSH alpha chain, and a beta subunit having a sequence of a non-human mammal FSH beta chain of the same species as the alpha chain, and wherein said alpha and beta subunits are covalently linked by a peptide linker. 
     
     
         7 . The method of  claim 6 , wherein the rFSH analog is an ungulate recombinant FSH analog. 
     
     
         8 . The method of  claim 7 , wherein the alpha subunit is a polypeptide comprising a sequence that is at least 95% homologous to SEQ ID NO 1 and the beta subunit is a polypeptide comprising a sequence that is at least 95% homologous to SEQ ID NO 2. 
     
     
         9 . The method of  claim 1 , wherein the non-human mammal is bovine, sheep, goat, cervid, yak, water buffalo, bison, antelope, gazelle, elk, reindeer, moose, bighorn sheep, giraffe, camelid, swine, equine, alpaca or vicuna. 
     
     
         10 . The method of  claim 9 , wherein the non-human mammal is a vicuna. 
     
     
         11 . The method of  claim 1 , wherein the rFSH comprises an amino acid sequence having at least 95% homology with SEQ ID NO 3. 
     
     
         12 . The method of  claim 9 , wherein the non-human mammal is a bovine. 
     
     
         13 . The method of  claim 1 , further comprising collecting oocytes from said non-human mammal near the time of ovulation and after rFSH analog administration. 
     
     
         14 . The method of  claim 1 , wherein said rFSH is injected in combination with at least one prostaglandin. 
     
     
         15 . The method of  claim 1 , wherein said rFSH is injected in combination with a progestagen based treatment. 
     
     
         16 . The method of  claim 1 , comprising:
 (a) providing a non-human mammal or a group of non-human mammals which has been treated to synchronize follicles;   (b) administering to said non-human mammal or group of non-human mammals one single dose of an rFSH analog at a dose range between about 0.01 μg and about 5 mg; and   (c) optionally, inseminating the non-human mammal or group of non-human mammals or collecting oocytes from the non-human mammal or group of non-human mammals near the time of ovulation and after administration step (b).   
     
     
         17 . The method of  claim 1 , comprising:
 (a) treating a non-human mammal or a group of non-human mammals to synchronize follicles;   (b) administering to said non-human mammal or group of non-human mammals one single dose of an rFSH analog at a dose range between about 0.01 μg and about 5 mg; and   (c) optionally, inseminating the non-human mammal or group of non-human mammals by artificial insemination or collecting oocytes from the non-human mammal or group of non-human mammals near the time of ovulation and after administration step (b).   
     
     
         18 . The method of  claim 16 , wherein follicle synchronization is obtained by hormonal treatment of the non-human mammal with a prostaglandin, a progestagen, and/or GnRH. 
     
     
         19 . The method of  claim 18 , wherein follicle synchronization is obtained by a combined administration of a progestagen and prostaglandin PGF2alpha. 
     
     
         20 . A method to increase reproductive performance in a bovine or group of bovine, wherein the method comprises:
 (a) administering to the bovine, or to at least two members of the group of bovine, a prostaglandin, progestagen, and/or GnRH in an amount effective to induce follicle synchronization; and   (b) administering to the follicle-synchronized bovine, in one single administration, between 10 μg and 1 mg of a recombinant FSH analog.